Meta-Analyses Reveal Who Should Be More Cautious of COVID-19

In April 2020, Chinese researchers at Weifang Medical University published the first peer-reviewed meta-analysis about medical comorbidities and COVID-19 disease severity. They screened several literature databases and retrieved 6 studies for analysis. All studies are of high quality with a Newcastle-Ottawa Scale (NOS) score of at least 6 points (see table below).

  • 6 studies researched hypertension, diabetes, and chronic obstructive pulmonary disease (COPD).
  • 5 studies examined liver disease.
  • 4 covered malignancy, renal disease, and cardiovascular disease.
  • 3 evaluated cerebrovascular [blood vessels] diseases.

Meta-Analysis Outcomes

COVID-19 patients with cerebrovascular diseases (OR: 3.89), cardiovascular diseases (OR: 2.93), hypertension (OR: 2.29), diabetes (OR: 2.47), and COPD (OR: 5.97) had an increased risk of disease exacerbation/progression, the researchers reported.

Odds ratio (OR) of 1 means neutral — wherein the occurrence of an event is neither increased nor decreased. OR >1 means an increased occurrence of an event. OR <1 means a decreased occurrence of an event.

To translate what they have reported, COVID-19 patients with cerebrovascular (or blood vessel) diseases have a 289% increased odds (or 3.89 times more likely) to progress into a more severe condition. Likewise for the rest:

  • Cerebrovascular disease: 289% increased odds (or 3.89 times more likely).
  • Cardiovascular disease: 193% increased odds (or 2.93 times more likely).
  • Hypertension: 129% increased odds (or 2.29 times more likely).
  • Diabetes: 147% increased odds (or 2.47 times more likely).
  • COPD: 497% increased odds (or 5.97 times more likely).
  • Liver disease, malignant tumor, or kidney disease: No significant correlation.

Liver disease, malignant tumor or kidney disease seems uninvolved in COVID-19 prognosis. “Our meta-analysis did not provide sufficient evidence that there was a correlation between liver disease, malignant tumor or kidney disease, and COVID-19 patients’ aggravation,” the authors explained.

“The meta-analysis identified hypertension, diabetes, COPD, cardiovascular disease, and cerebrovascular disease as significant risk factors for COVID-19 patients,” they concluded. “The knowledge of these factors can better define those COVID-19 patients at higher risk, and thus allow a more targeted and specific approach to prevent those deaths.”

Physicians should be particularly careful about COVID-19 patients with COPD, as the Chinese further emphasized,

Other Similar Meta-Analyses

The third related meta-analysis, published May 11, by researchers at University College London looked at COPD only. This time, 15 studies were examined and the pooled sample size was 2473 cases. COPD patients had nearly 2x increased risk of severe COVID-19 than non-COPD (63% vs. 33.4% prevalence). A bonus is that they also analyzed smoking data, showing that, “Current smokers were 1.45 times more likely to have severe complications compared to former and never smokers.”

Another published meta-analysis on 13th May investigating the relationship between smoking and COVID-19 had a similar conclusion. Scientists at the University of California San Francisco synthesized 19 peer-reviewed papers — totaling 11,590 COVID-19 patients. “Our analysis confirms that smoking is a risk factor for progression of COVID-19, with smokers having 1.91-times the odds of progression in COVID-19 severity than never smokers,” they wrote.

Why Is COPD (and Smoking) Particularly Bad?

Chronic obstructive pulmonary disease (COPD) refers to the lung damage wherein air sacs are destroyed. This leads to poor oxygen-carbon dioxide gas exchange — making breathing difficult. COPD is largely a lifestyle disease with no cure, of which 85–90% of cases are caused by habitual cigarette smoke.

Researchers at the University of British Columbia found that lung cells of cigarette smokers and COPD patients have higher expression of the ACE2 receptor, which SARS-CoV-2 (the virus that causes COVID-19) use to enter cells. “We found that patients with COPD and people who are still smoking have higher levels of ACE-2 in their airways, which might put them at an increased risk of developing severe COVID-19 infections,” they said.

The increased expression of ACE2 receptors is actually a defense mechanism in response to damaged air sacs. “While the up-regulation of ACE-2 may be useful in protecting the host against acute lung injury, chronically, this may predispose individuals to increased risk of coronavirus infections, which uses this receptor to gain entrance into epithelial cells,” the authors explained.

The good news is that it’s never too late to quit smoking. “We also found that former smokers had similar levels of ACE-2 to people who had never smoked,” the researchers added. “This suggests that there has never been a better time to quit smoking to protect yourself from COVID-19.”

Meta-Analyses Limitations

It should be noted that all studies have limitations. The Chinese authors of the peer-reviewed meta-analysis do acknowledge the small sample size of their pooled studies, and that some patients have multiple medical comorbidities. Still, these drawbacks are by no means profound; they do not negate the fact that the results are statistically significant and the ramifications of having only one comorbidity.

A major caveat, however, which the authors did not mention, is that those studies did not separate their analyses based on the severity, stages, or subtypes of the medical comorbidity. For example, it’s unclear how each stage of heart failure — A, B, C, or D — affects the risk of COVID-19 progression. Or how the dosage of cigarette smoke influences COVID-19 severity.

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